Diabetic retinopathy (DR), diabetic nephropathy (DN), and other microvascular complications of diabetes are caused by hyperglycemia, although genetic factors play an important role. Intensive glycemic control has been shown to delay the onset or progression of DR and DN in diabetic patients (The Diabetes Control and Complications Trial Research Group, N. Engl. J. Med. 329, 977-86. (1993); UK Prospective Diabetes Study (UKPDS) Group. Lancet 352, 837-53. (1998)). However, once the pathology of DR has been established, clinical studies have shown that it is very difficult to stop or reverse the progression of the vascular pathologies of DR or DN. The Epidemiology of Diabetes Interventions and Complications (EDIC) study, which followed type 1 diabetic patients for over ten years after the Diabetes Control and Complications Trial (DCCT) study ended, showed that prevalence of retinopathy and nephropathy continue to develop at a greater rate in those patients who initially had poor glycemic control. This occurred even after ten years of sharing similar glycemic control between the intensive and standard control groups (The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. JAMA 287, 2563-9 (2002); The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. JAMA 290, 2159-67 (2003)). Surprisingly, the prevalence of DR and DN continued to diverge between these two groups, hence the phrase, “metabolic memory.”